Alexander disease is a rare and generally fatal disorder of the CNS that primarily affects young children. Recent genetic studies have identified heterozygous missense mutations in the astrocyte intermediate filament glial fibrillary acidic protein (GFAP) as the major cause of this disease. To begin a search for potential treatments of this devastating disease, the investigator proposes to screen a library of drugs that are already FDA-approved to identify compounds that suppress expression of GFAP. He will evaluate changes in GFAP expression at the level of both protein and gene transcription, in glioma cell lines (Specific Aim 1), primary cultures of astrocytes (Specific Aim 2), and organotypic explant cultures of spinal cord (Specific Aim 3). In future years using mice that express the same mutant GFAPs found in human patients (generated as part of another project) can then be tested candidate drugs identified as part of this screen. By restricting the focus to the FDA-approved list, successful identification of GFAP-suppressing drugs could offer immediate therapeutic benefit to Alexander disease patients.